Bernard de Bono

Bernard de Bono
University College London | UCL

MD PhD

About

93
Publications
12,297
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7,719
Citations
Additional affiliations
April 2014 - present
University of Auckland
Position
  • Principal Investigator

Publications

Publications (93)
Preprint
Full-text available
Birth defects are functional and structural abnormalities that impact 1 in 33 births in the United States. Birth defects have been attributed to genetic as well as other factors, but for most birth defects there are no known causes. Small molecule drugs, cosmetics, foods, and environmental pollutants may cause birth defects when the mother is expos...
Article
Full-text available
The stimulating peripheral activity to relieve conditions (SPARC) program is a US National Institutes of Health-funded effort to improve our understanding of the neural circuitry of the autonomic nervous system (ANS) in support of bioelectronic medicine. As part of this effort, the SPARC project is generating multi-species, multimodal data, models,...
Article
Full-text available
We present (i) the ApiNATOMY workflow to build knowledge models of biological connectivity, as well as (ii) the ApiNATOMY TOO map, a topological scaffold to organize and visually inspect these connectivity models in the context of a canonical architecture of body compartments. In this work, we outline the implementation of ApiNATOMY’s knowledge rep...
Preprint
Full-text available
The Stimulating Peripheral Activity to Relieve Conditions (SPARC) program is a US National Institutes of Health-funded effort to improve our understanding of the neural circuitry of the autonomic nervous system in support of bioelectronic medicine. As part of this effort, the SPARC project is generating multi-species, multimodal data, models, simul...
Article
Full-text available
The Data and Resource Center (DRC) of the NIH-funded SPARC program is developing databases, connectivity maps, and simulation tools for the mammalian autonomic nervous system. The experimental data and mathematical models supplied to the DRC by the SPARC consortium are curated, annotated and semantically linked via a single knowledgebase. A data po...
Article
Full-text available
Sialic acid-binding immunoglobulin-like lectin (Siglec)-15 has recently been identified as a critical tumour checkpoint, augmenting the expression and function of programmed death-ligand 1. We raised a monoclonal antibody, A9E8, specific for Siglec-15 using phage display. A9E8 stained myeloid leukaemia cell lines and peripheral cluster of different...
Preprint
Full-text available
The Data and Resource Center (DRC) of the NIH-funded SPARC program is developing databases, connectivity maps and simulation tools for the mammalian autonomic nervous system. The experimental data and mathematical models supplied to the DRC by the SPARC consortium are curated, annotated and semantically linked via a single knowledgebase. A data por...
Article
Full-text available
We present a framework for the topological and semantic assembly of multiscale physiology route maps. The framework, called ApiNATOMY, consists of a knowledge representation (KR) model and a set of knowledge management (KM) tools. Using examples of ApiNATOMY route maps, we present a KR format that is suitable for the analysis and visualization by K...
Article
Full-text available
Background: Mathematics and Phy sics-based simulation models have the potential to help interpret and encapsulate biological phenomena in a computable and reproducible form. Similarly, comprehensive descriptions of such models help to ensure that such models are accessible, discoverable, and reusable. To this end, researchers have developed tools...
Preprint
Motivation: Mathematics and physics based computational models have the potential to help interpret and encapsulate biological phenomena in a computable and reproducible form. Similarly, comprehensive descriptions of such models encoded in computable form help to ensure that such models are accessible, discoverable, and reusable. To this end, resea...
Article
We introduce, and provide examples of, the application of the bond graph formalism to explicitly represent biophysical processes between and within modular biological compartments in ApiNATOMY. In particular, we focus on modelling scenarios from acid-base physiology to link distinct process modalities as bond graphs over an ApiNATOMY circuit of mul...
Article
Full-text available
Neurodegenerative disorders such as Parkinson’s and Alzheimer’s disease are devastating and costly illnesses, a source of major global burden. In order to provide successful interventions for patients and reduce costs, both causes and pathological processes need to be understood. The ApiNATOMY project aims to contribute to our understanding of neur...
Article
Neurodegenerative disorders such as Parkinson’s and Alzheimer’s disease are devastating and costly illnesses, a source of major global burden. In order to provide successful interventions for patients and reduce costs, both causes and pathological processes need to be understood. The ApiNATOMY project aims to contribute to our understanding of neur...
Article
Computational models of many aspects of the mammalian cardiovascular circulation have been developed. Indeed, along with orthopaedics, this area of physiology is one that has attracted much interest from engineers, presumably because the equations governing blood flow in the vascular system are well understood and can be solved with well-establishe...
Article
Full-text available
The goal of developing therapies and dosage regimes for characterized subgroups of the general population can be facilitated by the use of simulation models able to incorporate information about inter-individual variability in drug disposition (pharmacokinetics), toxicity and response effect (pharmacodynamics). Such observed variability can have mu...
Article
Knowledge of multiscale mechanisms in pathophysiology is the bedrock of clinical practice. If quantitative methods, predicting patient-specific behaviour of these pathophysiology mechanisms, are to be brought to bear on clinical decision-making, the Human Physiome community and Clinical community must share a common computational blueprint for path...
Article
Full-text available
Reconstructing and understanding the Human Physiome virtually is a complex mathematical problem, and a highly demanding computational challenge. Mathematical models spanning fromthemolecular level through to whole populations of individuals must be integrated, then personalized. This requires interoperability with multiple disparate and geographica...
Chapter
This chapter discusses the development and use of standards, tools, and software for computational modeling of the human body, including the concept of a physiology circuit board, and how these could be linked to the encoding of patient data in electronic health records (EHR) standards such as openEHR. It describes the use of openEHR Archetypes to...
Article
Full-text available
Since the decoding of the Human Genome, techniques from bioinformatics, statistics, and machine learning have been instrumental in uncovering patterns in increasing amounts and types of different data produced by technical profiling technologies applied to clinical samples, animal models, and cellular systems. Yet, progress on unravelling biologica...
Article
Depuis le développement de l’anatomie humaine moderne il y a 5 siècles, art et anatomie ont toujours été liés. Les premiers anatomistes, Vésale – De Vinci, étaient des artistes reconnus. Cependant, de nos jours, les représentations anatomiques ont pris une autre direction grâce aux représentations tridimensionnelles et à la modélisation. Bien que c...
Article
We identified a novel, evolutionarily conserved receptor encoded within the human leukocyte receptor complex and syntenic region of mouse chromosome 7, named T cell-interacting, activating receptor on myeloid cells-1 (TARM1). The transmembrane region of TARM1 contained a conserved arginine residue, consistent with association with a signaling adapt...
Article
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This is the author accepted manuscript. It is currently under an indefinite embargo pending publication of the final version.
Article
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A key challenge for the physiology modeling community is to enable the searching, objective comparison and, ultimately, re-use of models and associated data that are interoperable in terms of their physiological meaning. In this work, we outline the development of a workflow to modularize the simulation of tissue-level processes in physiology. In p...
Conference Paper
Full-text available
This paper briefly outlines the aim, the objectives, the architecture and the main building blocks of the ongoing large scale integrating transatlantic research project CHIC (http://chic-vph.eu/).
Conference Paper
Full-text available
Physiology experts deal with complex biophysical relation-ships, across multiple spatial and temporal scales. Automating the dis-covery of such relationships, in terms of physiological meaning, is a key goal to the physiology community. ApiNATOMY is an effort to provide an interface between the physiology expert's knowledge and all ranges of data r...
Article
Full-text available
Blood cells derive from hematopoietic stem cells through stepwise fating events. To characterize gene expression programs driving lineage choice, we sequenced RNA from eight primary human hematopoietic progenitor populations representing the major myeloid commitment stages and the main lymphoid stage. We identified extensive cell type–specific expr...
Article
Phylogenetic analyses based on models of molecular sequence evolution have driven to industrial scale the generation, cataloguing and modelling of nucleic acid and polypeptide structure. The recent application of these techniques to study the evolution of protein interaction networks extends this analytical rigour to the study of nucleic acid and p...
Article
Treemapping is a method for displaying hierarchical data using nested rectangles. Each branch of the tree is given its rectangle, which then is tiled with smaller rectangles representing sub-branches. A node's shape has an area proportional to a specified dimension of the data. To create a treemap, one must define a tiling algorithm, i.e., a way to...
Article
Full-text available
Large biomedical simulation initiatives, such as the Virtual Physiological Human (VPH), are substantially dependent on controlled vocabularies to facilitate the exchange of information, of data and of models. Hindering these initiatives is a lack of a comprehensive ontology that covers the essential concepts of the simulation domain. We propose a f...
Article
Full-text available
Histology information management relies on complex knowledge derived from morphological tissue analyses. These approaches have not significantly facilitated the general integration of tissue- and molecular-level knowledge across the board in support of a systematic classification of tissue function, as well as the coherent multi-scale study of phys...
Article
Full-text available
Background In this paper, we use: i) formalised anatomical knowledge of connectivity between body structures and ii) a formal theory of physiological transport between fluid compartments in order to define and make explicit the routes followed by proteins to a site of interaction. The underlying processes are the objects of mathematical models of p...
Article
Full-text available
European funding under Framework 7 (FP7) for the virtual physiological human (VPH) project has been in place now for 5 years. The VPH Network of Excellence (NoE) has been set up to help develop common standards, open source software, freely accessible data and model repositories, and various training and dissemination activities for the project. It...
Article
A wealth of potentially shareable resources, such as data and models, is being generated through the study of physiology by computational means. Although in principle the resources generated are reusable, in practice, few can currently be shared. A key reason for this disparity stems from the lack of consistent cataloguing and annotation of these r...
Article
A significant proportion of biomedical resources carries information that cross references to anatomical structures across multiple scales. To improve the visualization of such resources in their anatomical context, we developed an automated methodology that produces anatomy schematics in a consistent manner,and provides for the overlay of anatomy-...
Conference Paper
The practice and research of biomedicine generates considerable quantities of data and model resources (DMRs). The RICORDO effort works closely with modelling communities in the physiology and pharmacology domains to provide a semantic interoperability framework that addresses obstacles to biomedical DMR sharing. The RICORDO framework adopts a core...
Article
Full-text available
The article presents an infrastructure for supporting the semantic interoperability of biomedical resources based on the management (storing and inference-based querying) of their ontology-based annotations. This infrastructure consists of: (i) a repository to store and query ontology-based annotations; (ii) a knowledge base server with an inferenc...
Article
Full-text available
Biomedical imaging has become ubiquitous in both basic research and the clinical context. Technology advances and the resulting multitude of imaging modalities have led to a sharp rise in the quantity and quality of such images. In addition, computational models are increasingly used to study biological processes involving spatio-temporal changes i...
Article
Full-text available
ABSTRACT: The practice and research of medicine generates considerable quantities of data and model resources (DMRs). Although in principle biomedical resources are re-usable, in practice few can currently be shared. In particular, the clinical communities in physiology and pharmacology research, as well as medical education, (i.e. PPME communities...
Article
Full-text available
Systems biology is an approach to biology that emphasizes the structure and dynamic behavior of biological systems and the interactions that occur within them. To succeed, systems biology crucially depends on the accessibility and integration of data across domains and levels of granularity. Biomedical ontologies were developed to facilitate such a...
Conference Paper
This work is part of a general treatment of physiological phenomena grounded on connectivity between anatomical compartments. As a number of immune-related mechanisms may be formally described in terms of white cell movement across body compartments, this paper is concerned with the representation of routes of connectivity in the immune system, foc...
Chapter
Systems biology provides a crucial platform for knowledge accumulation of signaling pathways, which control platelet functions or their inhibition. It assists in interpreting the impact of congenital and acquired defects that result in an increased tendency to bleed.
Article
Within the healthy population, there is substantial, heritable, and interindividual variability in the platelet response. We explored whether a proportion of this variability could be accounted for by interindividual variation in gene expression. Through a correlative analysis of genome-wide platelet RNA expression data from 37 subjects representin...
Article
Full-text available
European funding under framework 7 (FP7) for the virtual physiological human (VPH) project has been in place now for nearly 2 years. The VPH network of excellence (NoE) is helping in the development of common standards, open-source software, freely accessible data and model repositories, and various training and dissemination activities for the pro...
Article
Full-text available
Platelet response to activation varies widely between individuals but shows interindividual consistency and strong heritability. The genetic basis of this variation has not been properly explored. We therefore systematically measured the effect on function of sequence variation in 97 candidate genes in the collagen and adenosine-diphosphate (ADP) s...
Article
In this study, we demonstrate the suitability of the vertebrate Danio rerio (zebrafish) for functional screening of novel platelet genes in vivo by reverse genetics. Comparative transcript analysis of platelets and their precursor cell, the megakaryocyte, together with nucleated blood cell elements, endothelial cells, and erythroblasts, identified...
Article
Full-text available
Reactome ("http://www.reactome.org":http://www.reactome.org) is an expert-authored, peer-reviewed knowledgebase of human reactions and pathways that functions as a data mining resource and electronic textbook. Its current release includes 2921 human proteins, 2871 reactions and 4167 literature citations. This curated dataset is integrated with a fu...
Article
Full-text available
The CD33-related sialic acid binding Ig-like lectins (CD33rSiglecs) are predominantly inhibitory receptors expressed on leukocytes. They are distinguishable from conserved Siglecs, such as Sialoadhesin and MAG, by their rapid evolution. A comparison of the CD33rSiglec gene cluster in different mammalian species showed that it can be divided into su...
Article
Full-text available
The published version of this article [1] inadvertently omitted a citation to the Nucleic Acids Research study in which Reactome was first described [2]. In addition, the author list included Dr Geeta Joshi-Tope. Upon her request, we are removing Dr Joshi-Tope as an author; a corrected author list has been provided with this Correction.
Article
Full-text available
Hematopoiesis is a carefully controlled process that is regulated by complex networks of transcription factors that are, in part, controlled by signals resulting from ligand binding to cell-surface receptors. To further understand hematopoiesis, we have compared gene expression profiles of human erythroblasts, megakaryocytes, B cells, cytotoxic and...
Article
Full-text available
Reactome (http://www.reactome.org) is an expert-authored, peer-reviewed knowledgebase of human reactions and pathways that functions as a data mining resource and electronic textbook. Its current release includes 2975 human proteins, 2907 reactions and 4455 literature citations. A new entity-level pathway viewer and improved search and data mining...
Article
The extent of platelet response to agonists varies between individuals and is to a large extent genetically controlled. Here we present the results of a systems biology study designed to define the association between sequence variation and platelet functional phenotype. The exons and flanking intronic regions of 98 genes, with known function in pl...
Article
In this study we demonstrate the suitability of the vertebrate Danio rerio (zebrafish) for functional screening of novel platelet genes in vivo by reverse genetics. Comparative transcript analysis of platelets and their precursor cell the megakaryocyte, together with nucleated blood cell elements, endothelial cells and erythroblasts, identified nov...
Article
Haematopoiesis is a carefully controlled process that is regulated by complex networks of transcription factors that are, in part, controlled by signals resulting from ligand binding to cell surface receptors. In order to further understand haematopoiesis, we have compared gene expression profiles of human erythroblasts, megakaryocytes, B-cells, cy...
Article
Full-text available
Sialic acid binding immunoglobulin-like lectins (Siglec) are important components of immune recognition. The organization of Siglec genes in different species is consistent with rapid selection imposed by pathogens. We studied SIGLEC11 genes in human, rodent, dog, cow and non-human primates. The lineages of SIGLEC11 genes in these species have unde...